Abstract
Compared to glycoproteins of healthy cells, glycoproteins of tumor cells are often aberrantly glycosylated. Thus, glycopeptide fragments of surface glycoproteins of tumor cells are of interest as tumorassociated antigens for the distinction between normal and tumor cells. Cancer immunotherapy directed at selectively targeting these tumor-associated glycoprotein structure alterations deficient glycosylation and, thus, exposure of peptide epitopes which are masked in normal cells is considered a promising approach for the treatment of cancer. For this purpose, glycoproteins from the mucin family are of particular interest. Mucins belong to a class of heavily O-glycosylated, high-molecular weight glycoproteins present on the surface of many epithelial cells. The mucin core protein consists of numerous tandem repeats rich in serine, threonine and proline. In their tumor-associated forms, epithelial mucins carry cryptic saccharide structures such as TN-, T-, sialyl-TN- and sialyl-T antigens and more complex oligosaccharides (e.g. Lewisy). In contrast to glycoproteins isolated from natural sources, synthetic glycopeptides can be obtained in high purity and with exactly defined structure. In this review, methodologies for the synthesis of mucin-type glycopeptides containing complex tumorassociated antigen structures are described. Due to the low immunogenicity often exhibited by synthetic tumor-associated glycopeptide antigens, their conjugation to carrier proteins or suitable T-cell epitopes is essential for the development of anti-tumor vaccines. The results of immunological evaluations of synthetic (glyco)peptides and oligosaccharides are described. Some of these synthetic vaccines show promising activities inducing proliferation of T-cells and cytotoxic T-cell responses.
Keywords: Glycopeptides, synthetic vaccines, biomimetic synthesis of O-glycosyl amino acids, tumor-associated antigens, MUC1 mucin, anti-tumor vaccines, solid-phase synthesis, glycopeptide protein conjugates
Current Cancer Drug Targets
Title: Synthetic Glycopeptides from the Mucin Family as Potential Tools in Cancer Immunotherapy
Volume: 6 Issue: 6
Author(s): Torsten Becker, Sebastian Dziadek, Sven Wittrock and Horst Kunz
Affiliation:
Keywords: Glycopeptides, synthetic vaccines, biomimetic synthesis of O-glycosyl amino acids, tumor-associated antigens, MUC1 mucin, anti-tumor vaccines, solid-phase synthesis, glycopeptide protein conjugates
Abstract: Compared to glycoproteins of healthy cells, glycoproteins of tumor cells are often aberrantly glycosylated. Thus, glycopeptide fragments of surface glycoproteins of tumor cells are of interest as tumorassociated antigens for the distinction between normal and tumor cells. Cancer immunotherapy directed at selectively targeting these tumor-associated glycoprotein structure alterations deficient glycosylation and, thus, exposure of peptide epitopes which are masked in normal cells is considered a promising approach for the treatment of cancer. For this purpose, glycoproteins from the mucin family are of particular interest. Mucins belong to a class of heavily O-glycosylated, high-molecular weight glycoproteins present on the surface of many epithelial cells. The mucin core protein consists of numerous tandem repeats rich in serine, threonine and proline. In their tumor-associated forms, epithelial mucins carry cryptic saccharide structures such as TN-, T-, sialyl-TN- and sialyl-T antigens and more complex oligosaccharides (e.g. Lewisy). In contrast to glycoproteins isolated from natural sources, synthetic glycopeptides can be obtained in high purity and with exactly defined structure. In this review, methodologies for the synthesis of mucin-type glycopeptides containing complex tumorassociated antigen structures are described. Due to the low immunogenicity often exhibited by synthetic tumor-associated glycopeptide antigens, their conjugation to carrier proteins or suitable T-cell epitopes is essential for the development of anti-tumor vaccines. The results of immunological evaluations of synthetic (glyco)peptides and oligosaccharides are described. Some of these synthetic vaccines show promising activities inducing proliferation of T-cells and cytotoxic T-cell responses.
Export Options
About this article
Cite this article as:
Becker Torsten, Dziadek Sebastian, Wittrock Sven and Kunz Horst, Synthetic Glycopeptides from the Mucin Family as Potential Tools in Cancer Immunotherapy, Current Cancer Drug Targets 2006; 6 (6) . https://dx.doi.org/10.2174/156800906778194577
DOI https://dx.doi.org/10.2174/156800906778194577 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Dihydropyrimidine Dehydrogenase Genotyping and Phenotyping for 5- Fluorouracil Dysmetabolism: Moving Towards Personalized Chemotherapy in Patients with Cancer
Current Pharmacogenomics and Personalized Medicine Difference Gel Electrophoresis: Application in Quantitative Proteomics Research
Current Proteomics Implications of Fibroblast Growth Factors (FGFs) in Cancer: From Prognostic to Therapeutic Applications
Current Drug Targets The Vitamin D/CYP24A1 Story in Cancer
Anti-Cancer Agents in Medicinal Chemistry Autoimmune Diseases in Gastroenterology
Current Pharmaceutical Design Angiotensin Converting Enzyme-2: A Doorway for SARS-CoV-2
Coronaviruses Magnetic Nanoparticles in Brain Disease Diagnosis and Targeting Drug Delivery
Current Nanoscience Functional Genomics: New Insights into the Function of Low Levels of Gene Expression in Stem Cells
Current Genomics 4-Hydroxynonenal in the Pathogenesis and Progression of Human Diseases
Current Medicinal Chemistry Energy Dependent Transport of Xenobiotics and Its Relevance to Multidrug Resistance
Current Cancer Drug Targets Diabetic Gastroenteropathy: Soothe the Symptoms or Unravel a Cure?
Current Diabetes Reviews In Vivo Treatment Efficacy of Essential Oil Isolated from Seeds of <i>Momordica charantia</i> in Streptozotocin-Induced Diabetes Mellitus
Recent Patents on Biotechnology MDA-7/IL-24-Based Cancer Gene Therapy: Translation from the Laboratory to the Clinic
Current Gene Therapy Interactions of Iron Oxide Nanoparticles with the Immune System: Challenges and Opportunities for their Use in Nano-oncology
Current Pharmaceutical Design Proteomics on Fixed Tissue Specimens – A Review
Current Proteomics Incretin Pharmacology: A Review of the Incretin Effect and Current Incretin-Based Therapies
Cardiovascular & Hematological Agents in Medicinal Chemistry Cellular Localisation of Chromogranins and Processed Products in the Diffuse Neuroendocrine System and Related Tumours
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents The Role of TNFSF15 in the Modulation of Neovascularization and Inflammation
Current Hypertension Reviews Cancer Stem Cells – Are Surface Markers Alone Sufficient?
Current Stem Cell Research & Therapy Expression Microarray Proteomics and the Search for Cancer Biomarkers
Current Genomics